Evaluation of DNA Methylation as a Target for Intraductal Therapy for Ductal Carcinoma in Situ of the Breast
Abstract
Ductal carcinoma in situ(DCIS), the preinvasive form of infiltrating ductal breast cancer, accounts for 20-30% of breast cancers and is treated surgically. In DCIS, the malignant cells are confined within the basement membrane. DCIS is a local disease, and so an ideal candidate for local therapies. DNA methylation is one mechanism for tumor suppressor gene inactivation. It is an early event in the course of malignant progression. Because methylation is a potentially reversible mechanism for tumor suppressor gene inactivation, it is an intriguing target for molecular therapeutics. Drugs, such as 5-azadeoxycytidine (DAC), are available that can reverse methylation changes and prevent neoplasia in vivo. Hypothesis: DNA Methylation is altered in DCIS aid is a therapeutic target for intraductal therapy. Specific Aim 1: Document the methylation status of tumor suppressor genes in DCIS. Specific Aim 2: Document the feasibility of an intraductal approach to DCIS. Specific Aim 3: Identify the dose(s) of DAC with biologic activity and acceptable side effects when delivered intraductally to patients with DCIS (phase I trial). The ultimate goal of this proposal is to evaluate DNA methylation as a target for intraductal therapy. The results of this study could revolutionize the way we treat DClS.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2004
- Accession Number
- ADA431965
Entities
People
- Kristin A. Skinner
Organizations
- New York University